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https://www.readbyqxmd.com/read/29470146/towards-an-effective-peripheral-visceral-analgesic-responding-to-the-national-opioid-crisis
#1
Michael Camilleri
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29467763/functional-role-of-transient-receptor-potential-channels-in-immune-cells-and-epithelia
#2
REVIEW
Mohammad Khalil, Korina Alliger, Carl Weidinger, Cansu Yerinde, Stefan Wirtz, Christoph Becker, Matthias Agop Engel
Transient receptor potential (TRP) ion channels are widely expressed in several tissues throughout the mammalian organism. Originally, TRP channel physiology was focusing on its fundamental meaning in sensory neuronal function. Today, it is known that activation of several TRP ion channels in peptidergic neurons does not only result in neuropeptide release and consecutive neurogenic inflammation. Growing evidence demonstrates functional extra-neuronal TRP channel expression in immune and epithelial cells with important implications for mucosal immunology...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29464560/transient-receptor-potential-trp-channels
#3
Amrita Samanta, Taylor E T Hughes, Vera Y Moiseenkova-Bell
Transient Receptor Potential (TRP) channels are evolutionarily conserved integral membrane proteins. The mammalian TRP superfamily of ion channels consists of 28 cation permeable channels that are grouped into six subfamilies based on sequence homology (Fig. 6.1). The canonical TRP (TRPC) subfamily is known for containing the founding member of mammalian TRP channels. The vanilloid TRP (TRPV) subfamily has been extensively studied due to the heat sensitivity of its founding member. The melastatin-related TRP (TRPM) subfamily includes some of the few known bi-functional ion channels, which contain functional enzymatic domains...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29463718/structure-of-full-length-human-trpm4
#4
Jingjing Duan, Zongli Li, Jian Li, Ana Santa-Cruz, Silvia Sanchez-Martinez, Jin Zhang, David E Clapham
Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+ -bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29462784/transient-receptor-potential-vanilloid-4-trpv4-activation-by-arachidonic-acid-requires-protein-kinase-a-mediated-phosphorylation
#5
Sheng Cao, Andriy Anishkin, Natalya S Zinkevich, Yoshinori Nishijima, Ankush Korishettar, Zhihao Wang, Juan Fang, David A Wilcox, David X Zhang
TRPV4 is a Ca2+-permeable channel of the transient receptor potential (TRP) superfamily activated by diverse stimuli including warm temperature, mechanical forces, and lipid mediators such as arachidonic acid (AA) and its metabolites. This activation is tightly regulated by protein phosphorylation carried out by various serine/threonine or tyrosine kinases. It remains poorly understood how phosphorylation differentially regulates TRPV4 activation in response to different stimuli. We investigated how TRPV4 activation by AA, an important signaling process in the dilation of coronary arterioles, is affected by protein kinase A (PKA)-mediated phosphorylation at S824...
February 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29438128/toxins-in-pain
#6
Fernanda C Cardoso, Mahadhi Hasan, Tianjiao Zhao, Richard J Lewis
PURPOSE OF REVIEW: Pain is a distressing protective sensory experience warning of actual or potential tissue damage. Natural toxins have evolved to exploit pain and related neuronal pathways to facilitate prey capture and for defence, often producing either numbness, paralysis or intense pain by selectively modulating ion channels and receptors in pain pathways. Understanding how toxins modulate pain pathways can enhance our understanding of the physiological and pathological basis of pain...
February 12, 2018: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/29435486/transient-receptor-potential-channels-trpm4-and-trpc3-critically-contribute-to-respiratory-motor-pattern-formation-but-not-rhythmogenesis-in-rodent-brainstem-circuits
#7
Hidehiko Koizumi, Tibin T John, Justine X Chia, Mohammad F Tariq, Ryan S Phillips, Bryan Mosher, Yonghua Chen, Ryan Thompson, Ruli Zhang, Naohiro Koshiya, Jeffrey C Smith
Transient receptor potential channel, TRPM4, the putative molecular substrate for Ca2+-activated nonselective cation current (ICAN), is hypothesized to generate bursting activity of pre-Bötzinger complex (pre-BötC) inspiratory neurons and critically contribute to respiratory rhythmogenesis. Another TRP channel, TRPC3, which mediates Na+/Ca2+ fluxes, may be involved in regulating Ca2+-related signaling, including affecting TRPM4/ICAN in respiratory pre-BötC neurons. However, TRPM4 and TRPC3 expression in pre-BötC inspiratory neurons and functional roles of these channels remain to be determined...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29427475/application-of-an-8-capsaicin-patch-normalizes-epidermal-trpv1-expression-but-not-the-decreased-intraepidermal-nerve-fibre-density-in-patients-with-brachioradial-pruritus
#8
M P Pereira, H Lüling, A Dieckhöfer, S Steinke, C Zeidler, K Agelopoulos, S Ständer
BACKGROUND: Topical capsaicin shows efficacy in the treatment of brachioradial pruritus, however its mechanisms of action remain unclear. OBJECTIVE: The effect of capsaicin on the epidermis (i.e. peripheral expression of non-neuronal sensory receptors on keratinocytes, morphological changes in innervation) is still unknown. We aimed to investigate the effect of topical capsaicin on keratinocyte expression of TRP channels and on the intraepidermal nerve fibre density (IENFD) in patients with brachioradial pruritus...
February 10, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29425510/direct-binding-between-pre-s1-and-trp-like-domains-in-trpp-channels-mediates-gating-and-functional-regulation-by-pip2
#9
Wang Zheng, Ruiqi Cai, Laura Hofmann, Vasyl Nesin, Qiaolin Hu, Wentong Long, Mohammad Fatehi, Xiong Liu, Shaimaa Hussein, Tim Kong, Jingru Li, Peter E Light, Jingfeng Tang, Veit Flockerzi, Leonidas Tsiokas, Xing-Zhen Chen
Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues...
February 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29410612/nav1-9-potentiates-oxidized-phospholipid-induced-trp-responses-only-under-inflammatory-conditions
#10
Corinna Martin, Carolin Stoffer, Milad Mohammadi, Julian Hugo, Enrico Leipold, Beatrice Oehler, Heike L Rittner, Robert Blum
Oxidized phospholipids (OxPL) like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29405580/in-vitro-and-in-vivo-characterization-of-modulation-of-the-vacuolar-cation-channel-trpy1-from-saccharomyces-cerevisiae
#11
Shin Hamamoto, Yasuo Mori, Isamu Yabe, Nobuyuki Uozumi
Saccharomyces cerevisiae possesses a transient receptor potential (TRP) channel homolog TRPY1 in its vacuolar membrane, considered to be an ancestral TRP channel. So far, studies have focused on the channel properties of TRPY1 but its regulation and physiological role remained to be elucidated. Here we investigated TRPY1 channel function in vitro and in vivo. Patch-clamp recording of TRPY1 in yeast vacuolar membranes showed that Ca2+ on the lumen side inhibited TRPY1-mediated channel activity, whereas luminal Zn2+ increased the currents...
February 6, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29401628/calmodulin-regulates-a-trp-channel-adf1-and-phospholipase-c-plc-to-mediate-elevation-of-cytosolic-calcium-during-acidic-stress-that-induces-deflagellation-in-chlamydomonas
#12
Qiong Wu, Kang Gao, Shuzhi Zheng, Xin Zhu, Yinwen Liang, Junmin Pan
Calcium has been implicated in the motility, assembly, disassembly, and deflagellation of the eukaryotic flagellum or cilium (exchangeable terms). Calmodulin (CaM) is known to be critical for flagellar motility; however, it is unknown whether and how CaM is involved in other flagella-related activities. We have studied CaM in Chlamydomonas, a widely used organism for ciliary studies. CaM is present in the cell body and the flagellum, with enrichment in the basal body region. Loss of CaM causes shortening of the nucleus basal body connector and impairs flagellar motility and assembly but not flagellar disassembly...
January 29, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29393634/molecular-interactions-between-a-fluoride-ion-channel-and-synthetic-protein-blockers
#13
Daniel L Turman, Abraham Z Cheloff, Alexis D Corrado, Jacob T Nathanson, Christopher Miller
Fluoride ion channels of the Fluc family selectively export F- ions to rescue unicellular organisms from acute F- toxicity. Crystal structures of bacterial Fluc channels in complex with synthetic monobodies, fibronectin-derived soluble β-sandwich fold proteins, show 2-fold symmetric homodimers with an antiparallel transmembrane topology. Monobodies also block Fluc F- current via a pore blocking mechanism. However, little is known about the energetic contributions of individual monobody residues to the affinity of the monobody-channel complex or whether the structural paratope corresponds to functional reality...
February 2, 2018: Biochemistry
https://www.readbyqxmd.com/read/29378958/trpv1-channels-and-the-progesterone-receptor-sig-1r-interact-to-regulate-pain
#14
Miguel Ortíz-Rentería, Rebeca Juárez-Contreras, Ricardo González-Ramírez, León D Islas, Félix Sierra-Ramírez, Itzel Llorente, Sidney A Simon, Marcia Hiriart, Tamara Rosenbaum, Sara L Morales-Lázaro
The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29373067/role-of-trp-channels-in-dinoflagellate-mechanotransduction
#15
J B Lindström, N T Pierce, M I Latz
Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences...
October 2017: Biological Bulletin
https://www.readbyqxmd.com/read/29359496/the-transient-receptor-potential-vanilloid-3-regulates-hypoxia-mediated-pulmonary-artery-smooth-muscle-cells-proliferation-via-pi3k-akt-signaling-pathway
#16
Qianlong Zhang, Yonggang Cao, Qian Luo, Peng Wang, Pilong Shi, Chao Song, Mingyao E, Jing Ren, Bowen Fu, Hongli Sun
OBJECTVES: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca2+ -permeant cation channels. In this study, we aim to investigate the role of TRPV3 in pulmonary vascular remodeling and PASMCs proliferation under hypoxia. MATERIALS AND METHODS: The expression of TRPV3 was evaluated in patients with pulmonary arterial hypertension (PAH) and hypoxic rats, using hematoxylin and eosin (H&E) and immunohistochemistry. In vitro, MTT assay, flow cytometry, Western blotting and immunofluorescence were performed to investigate the effects of TRPV3 on proliferation of PASMCs...
January 22, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29344776/dawning-of-a-new-era-in-trp-channel-structural-biology-by-cryo-electron-microscopy
#17
REVIEW
M Gregor Madej, Christine M Ziegler
Cryo-electron microscopy (cryo-EM) permits the determination of atomic protein structures by averaging large numbers of individual projection images recorded at cryogenic temperatures-a method termed single-particle analysis. The cryo-preservation traps proteins within a thin glass-like ice layer, making literally a freeze image of proteins in solution. Projections of randomly adopted orientations are merged to reconstruct a 3D density map. While atomic resolution for highly symmetric viruses was achieved already in 2009, the development of new sensitive and fast electron detectors has enabled cryo-EM for smaller and asymmetrical proteins including fragile membrane proteins...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29323279/structural-basis-of-trpv5-channel-inhibition-by-econazole-revealed-by-cryo-em
#18
Taylor E T Hughes, David T Lodowski, Kevin W Huynh, Aysenur Yazici, John Del Rosario, Abhijeet Kapoor, Sandip Basak, Amrita Samanta, Xu Han, Sudha Chakrapani, Z Hong Zhou, Marta Filizola, Tibor Rohacs, Seungil Han, Vera Y Moiseenkova-Bell
The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29311301/trpm4-and-trpm5-are-both-required-for-normal-signaling-in-taste-receptor-cells
#19
Debarghya Dutta Banik, Laura E Martin, Marc Freichel, Ann-Marie Torregrossa, Kathryn F Medler
Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice have a reduced, but not abolished, ability to detect stimuli, suggesting that a TRPM5-independent pathway also contributes to these signals. Here, we identify a critical role for the sodium-selective TRP channel TRPM4 in taste transduction...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29306760/effect-of-acetaminophen-on-osteoblastic-differentiation-and-migration-of-mc3t3-e1-cells
#20
Yoshihiro Nakatsu, Fumio Nakagawa, Sen Higashi, Tomoko Ohsumi, Shunji Shiiba, Seiji Watanabe, Hiroshi Takeuchi
BACKGROUND: N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear...
July 15, 2017: Pharmacological Reports: PR
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